The objective of this study is to evaluate the use of intraoperative hyperthermia (IOHT) in combination with intraoperative radiation therapy (IORT) for the treatment of locally unresectable or recurrent pancreatic and colorectal carcinomas. There are three components of the study which are necessary to meet this objective. First, our experience with single element ultrasound transducers in heating large, complexly shaped and deep seated tumors has emphasized the need for the development of a hyperthermia system with multiple element flexible transducers with the power to each element under computer control. Thus, we plan to develop a flexible, multi-element ultrasound transducer hyperthermia system with adequate thermometry to allow computer monitored individual element power control. Second, normal tissues are tolerant to temperatures up to 42degrees- 44degreesC for relatively long periods of time depending on the tissue type. However, thermal enhancement ratios have not been established to evaluate the effect of combining large single doses of radiation with hyperthermia on many normal tissues including peripheral nerves. Since the intraoperative use of radiation with hyperthermia allows for the retrac- tion, resection, bypass or defunctionalization of nearly all significant normal structures except for peripheral nerves without unacceptable morbidity, a knowledge of the tolerance of peripheral nerves to these forms of therapy is essential to aid in the assessment of potential risks and benefits in human clinical trials. Thus, a second component of the study will be performed in dogs to evaluate the tolerance of peripheral nerves to IORT and IOHT, both alone and in combination. Thirdly, approximately 18 months after the start of the grant, when the first prototype multi-element transducers are available and preliminary data from the nerve studies has been obtained, we will initiate a Phase 1 trial of combination IORT and IOHT therapy utilizing the individual element power controlled multi- element transducer in patients with unresectable or recurrent pancreatic and colorectal carcinomas. We plan to treat these tumors with 1500 to 1750 cGy IORT and IOHT treatments of 43degreesC or greater for 60 minutes. This Phase 1 trial will evaluate the performance of the new multi-element transducer system and the feasibility and toxicity of this combined therapy along with accrual capability, techniques for determining therapeutic efficacy and stratification in preparation for a Phase 2 trial of local tumor control that will combine IORT with IOHT at varying thermal doses. The engineering development and clinical trial components of this study will be performed at the Darthmouth-Hitchcock Medical Center, and the animal peripheral nerve tolerance component will be performed at the Colorado State University Veterinary Teaching Hospital.